Similar to other nuclear hormone receptors, PPAR d heterodimerizes with retinoid X receptor and exerts its effects via regulation of gene transcription upon binding of ligand. The best-characterized role for PPAR d to date is to regulate lipid metabolism and energy homeostasis, such as AbMole Succinylsulfathiazole inducing reverse cholesterol transport, elevating high-density lipoprotein, increasing fatty acid oxidation and energy uncoupling. In addition, PPAR d is also implicated in embryo implantation, wound healing, inflammatory response, endothelial cell proliferation, angiogenesis, skin cancer and colorectal carcinogenesis. In contrast to the well-characterized roles of PPAR d in metabolic and energetic homeostasis, the role of PPAR d in colorectal carcinogenesis remains uncertain. Some studies provide evidences that PPAR d promotes tumorigenesis while others yield conflicting results, as we previously reviewed. Recently, we successfully established the PPAR d-knockdown models of colon cancer cell lines by lentivirus-mediated RNA interfering. We found that PPAR d knockdown significantly induced less differentiation and promoted proliferation of these cells. These findings indicate that PPAR d may play a tumor suppressor role by facilitating the differentiation and inhibiting the proliferation of colon cancer. However, there still lacks of in vivo experiment to testify these in vitro findings. To more rigorously define PPAR d??s role in colorectal carcinogenesis, we examined the effect of PPAR d knockdown on the nude mice xenografts established with KM12C cells in the present study. In the present study, we found that the xenografts in PPAR dsilenced group grew significantly faster with less differentiation, promoted cell proliferation while similar apoptosis index and increased VEGF compared with those of PPAR d-normal group, regardless of bevacizumab treatment. Administration of PPAR d agonist significantly decreased VEGF expression in PPAR dnormal KM12C cells, while didn??t affect that of PPAR d-silenced cells. These findings demonstrate that, knockdown of PPAR d promotes the growth of colon cancer by lessening the differentiation and promoting the proliferation as well as VEGF expression of tumor cells in vivo, and reduces tumor sensitivity to bevacizumab. These results support a suppressor role of PPAR d in the pathogenesis of colon cancer. In the present study, our finding that the xenografts in mice grew significantly larger and heavier after PPAR d knockdown indicates that PPAR d may attenuate tumor growth in vivo. In accordance to this finding, recent studies show that the colon polyp formation was significantly greater in PPAR d-deficient mice as compared with wild-type animals. In contrast to these observations, Park et al. reported that PPAR d-null HCT-116 cells had a decreased ability to form xenografts in nude mice. Another study concluded that PPAR d is dispensable for polyp formation in the colon of APCmin mice. However, these conclusions were based on the analysis of less than 6 mice, with limited statistical power.